Direct-acting antivirals for chronic Hepatitis C are effective and safe: an observational study in Londrina/PR

Abstract This study aimed to evaluate the effectiveness and safety of direct-acting antivirals in a Unified Health System pharmacy of Londrina, Brazil. A descriptive observational study was performed from June 2017 to June 2018. Sociodemographic, clinical, and therapeutic variables of patients were collected from secondary data sources. Effectiveness was evaluated by sustained virologic response (SVR) and safety was evaluated by adverse events (AEs) and drug interactions (DIs). The mean population (N=30) was 56.6±11.3 years old and almost all patients had comorbidities (93.3%) and concomitant drugs (96.7%). Effectiveness evaluation was possible in 17 patients, and all of them (100.0%) achieved SVR. Eighteen patients (60.0%) reported 38 AEs, mostly mild, such as stomach symptoms and headache. No statistical relation was found between AE occurrence and treatment duration, Ribavirin use, number of comorbidities or number of concomitant drugs. A total of 48 DIs were reported, 18 being severe, and were managed by the pharmacist. The study indicates that the treatment was effective and safe.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

Case for diagnosis. Sclerodermiform manifestations of porphyria cutanea tarda secondary to hepatitis C

Abstract: A 63-year-old black female patient with blisters and exulcerations on the face, neck, upper limbs, and subsequent evolution with hypochromic sclerotic areas and alopecia, is reported. Chronic hepatitis C and presence of high levels of porphyrins in urine were demonstrated. There was complete remission with the use of hydroxychloroquine, photoprotection, and treatment of hepatitis. Significant sclerodermoid involvement of the skin as a manifestation of porphyria cutanea tarda secondary to hepatitis C emphasizes the importance of diagnostic suspicion regarding skin manifestation in order to indicate the appropriate therapy, and to minimize the hepatic morbidity.

Bioimpedância: nova abordagem para detecção não invasiva da fibrose hepática - estudo piloto / Bioimpedance: new approach to non-invasive detection of liver fibrosis - a pilot study

ABSTRACT BACKGROUND: Fibrosis are common structural hepatic change in patients with chronic hepatitis. Liver biopsy is the gold standard for determining the extent of liver fibrosis. Considering the technical difficulties and cost, improvements in non-invasive screening tools are greatly needed. Bioimpedance have been shown to be safe to evaluate tissue fibrosis. OBJECTIVE: To assess the utility of using monofrequential bipolar bioimpedance for the detection of severity of liver fibrosis consistent with chronic viral hepatitis C infections. METHODS: One hundred and ten patients were studied prospectively and formed two groups according to the lab tests results for the detection of HCV, ALT and AST: Group 1 Control (n=50 healthy patients with HCV negative and with ALT and AST values within the normal clinical range) and Group 2 Positive (n=60 patients positive for anti-HCV positive) which were biopsied. All patients underwent an examination with an Electro Sensor Complex, bioimpedance technology. To compare the groups 1 and 2, the ROC curves was used to determine the specificity and sensitivity of the bioimpedance to detect liver fibrosis. To identify liver fibrosis severity the Group 2 Positive was subdivided according to the liver biopsy results (Metavir fibrosis score) into: Sub Group 2A (F0-F1 n=25) - patients without or with minimal portal fibrosis and Sub Group 2B (F3-F4 n=20) patients with numerous septa/cirrhosis. A statistical analysis was conducted to analyze the bioimpedance data differences in delta of the conductance. RESULTS: From the comparison between Groups 1 and 2: 1) The delta value for conductance in the pathway representing the right foot-left hand minus left hand-right foot demonstrated a sensitivity of 85% and a specificity of 78% with a cutoff value ≤5 and P=0.0001. 2) For the comparison between Sub Group 2A (Metavir F0+F1) and Sub Group 2B (Metavir F3+F4), the neural network for the Electro Sensor Complex data demonstrated a sensitivity of 85% and a specificity of 72% with a cutoff probability >50% and P=0.001. AUCROC=0.81. CONCLUSION: Bioimpedance technology had good level sensitivity and acceptable specificity for detecting liver fibrosis using delta of the conductance. There is a potential for the use of bioimpedance technology as non-invasive approaches for screening of liver fibrosis.

RESUMO CONTEXTO: A fibrose é uma alteração hepática estrutural comum em pacientes com hepatite crônica. A biópsia hepática é o padrão ouro para determinar a extensão da fibrose hepática. Considerando as dificuldades técnicas e os custos, melhorias em ferramentas de rastreio não-invasivas são bastante necessárias. A tecnologia bioimpedância tem se mostrado ser segura para avaliar fibrose tecidual. OBJETIVO: Avaliar a utilidade do uso da bioimpedância bipolar para detectar a severidade da fibrose hepática compatível com a hepatite viral B e C. MÉTODOS: Cento e dez pacientes foram estudados, prospectivamente e dois grupos foram formados de acordo com os resultados dos testes laboratoriais para a detecção de HCV, ALT e AST: Grupo 1 Controle (n=50 pacientes saudáveis com HCV negativos e com valores de ALT e AST dentro do padrão de normalidade) e Grupo 2 Positivo (n=60 pacientes positivos para a infecção viral anti-VHC ou HBsAg positiva) que foram biopsiados. Todos os pacientes foram submetidos a um exame com o Electro Sensor Complex, que utiliza a bioimpedância bipolar. Para comparar os Grupos 1 e 2, a curva ROC foi utilizada para determinar a especificidade e sensibilidade da bioimpedância em detectar a fibrose hepática. Para identificar a severidade da fibrose hepática, o Grupo 2 Positivo foi subdividido de acordo com os resultados da biópsia (escore Metavir) em: Sub Grupo 2A (F0-F1 n=25 ) - pacientes sem ou com fibrose portal mínima e Sub Grupo 2B (F3-F4 n=20) pacientes com numerosos septos/cirrose. A análise estatística foi realizada para analisar as diferenças dos valores delta de condutância da bioimpedância. RESULTADOS: A comparação entre os Grupos 1 e 2 mostrou: 1) O valor delta de condutância na via do pé direito à mão esquerda menos o valor do delta da mão esquerda ao pé direito demonstrou uma sensibilidade de 85% e uma especificidade de 78%, com um valor de corte ≤5 e P=0,0001. 2). Na comparação entre o Sub Grupo 2A (Metavir F0+F1) e o Sub Grupo 2B (Metavir F3 + F4), a rede neural para os dados aferidos pelo Electro Sensor Complex demonstrou uma sensibilidade de 85% e uma especificidade de 72%, com um corte de probabilidade >50% P=0,001 e AUCROC=0,81. CONCLUSÃO: Bioimpedância apresentou boa sensibilidade e aceitável especificidade para a detecção da fibrose hepática utilizando o delta da condutância da bioimpedância. Existe um potencial para o uso da bioimpedância como abordagens não-invasivas para o rastreamento da fibrose hepática.

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C

OBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

Transient elastography and APRI score: looking at false positives and false negatives. Diagnostic performance and association to fibrosis staging in chronic hepatitis C

Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis.

LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.

Hepatic peroxisome proliferator-activated receptor γ and α-mRNA expression in HCV-infected adults is decreased by HIV co-infection and is also affected by ethnicity

OBJECTIVE: To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.

Indução do padrão citoplasmático em forma de "bastões e anéis" através do tratamento da hepatite C: relato de caso / Induction of cytoplasmic pattern in the form of "rods and rings" through the treatment of hepatitis C: a case report

Paciente do sexo feminino, queixando-se de astenia e dor em hipogastro, foi admitida no pronto-socorro do Hospital Universitário do Oeste do Paraná (HUOP). Durante a anamnese relatou tratamento de infecção crônica pelo vírus da hepatite C (VHC) com inteferon peguilado e ribavirina. Dentre os exames laboratoriais solicitados, a pesquisa de autoanticorpos contra antígenos celulares (PAAC-HEp-2), conhecido tradicionalmente como fator antinúcleo (FAN), apresentou fluorescência em forma de bastões e/ou anéis no citoplasma das células. Esse padrão é caracterizado por bastões de 3-10 µm e anéis com 2-5 µm de diâmetro espalhados através do citoplasma da célula. Portanto, esse novo padrão tem sido designado como "bastões e anéis" (traduzido do inglês: Rods and Rings, RR). O alvo antigênico dessa reação foi identificado como inosina-5'-monofosfato desidrogenase tipo 2 (IMPDH2) que é uma enzima chave na síntese de nucleotídeos púricos. A enzima IMPDH2 agregada ou modificada em forma de RR nos pacientes tratados com ribavirina pode tornar-se antigênica e induzir uma resposta autoimune. É possível que o interferon alfa estimule a ocorrência de reatividade anti-RR aparentemente induzida pela ribavirina. Até o momento não se sabe por que o padrão RR em células HEp-2 ocorrem apenas em uma fração de pacientes portadores do VHC. Os dados apresentados em trabalhos anteriores possibilitam afirmar que esses anticorpos associados ao padrão RR estão fortemente relacionados com o tratamento da hepatite C. Além disso, pode-se afirmar que a ocorrência de reatividade anti-RR é promovida pela terapia combinada com interferon alfa e ribavirina.

Female patient, complaining of weakness and pain in hypogastric, was admitted to the emergency department of the University Hospital of the West of Paraná (HUOP). During the interview reported treatment of chronic infection with hepatitis C virus (HCV) with peginterferon and ribavirin. Among the laboratory tests ordered, the search for self-antibodies against cellular antigens, traditionally known as antinuclear factor, showed fluorescence shaped like rods and/or rings in the cytoplasm of cells. This study attempts to clarify the relationship between this pattern not yet completely understood and the clinical picture of the patient. This pattern is characterized by 3–10 µm rods or rings with 2–5 µm in diameter scattered throughout the cytoplasm of the cell. Therefore, this new standard has been designated as "rods and rings" (RR). The antigenic target of this reaction was identified as inosine-5'-monophosphate dehydrogenase type 2 (IMPDH2) which is a key enzyme in the synthesis of purine nucleotides. The IMPDH2 enzyme aggregated or modified shaped RR in those patients treated with ribavirin may become antigenic and induce an autoimmune response. It is possible that interferon alpha stimulates the occurrence of anti-RR reactivity apparently induced by ribavirin. So far it is not known why the standard RR in HEp2 cells occurs only in a fraction of patients with HCV. Previous studies presented in this paper allow affirming that these antibodies associated with the standard RR are strongly related to hepatitis C. Moreover, it can be stated that the occurrence of anti-RR reactivity is promoted by combination therapy with interferon and ribavirin.

Association of aaffeine intake and liver fibrosis in patients with chronic hepatiti cc / Associação do consumo da cafeína com o grau de fibrose hepática em pacientes com hepatite C crônica

Background Caffeine consumption has been associated to decreased levels of liver enzymes and lower risk of fibrosis in patients with hepatitis C virus. Objectives This study aimed to evaluate the association between caffeine consumption and inflammatory activity or degree of liver fibrosis in patients with hepatitis C virus infection. Methods A cross-sectional study of patients with chronic hepatitis C virus infection treated in an outpatient Gastroenterology Unit of Santa Casa Hospital (Porto Alegre - Brasil). Patients were interviewed regarding the consumption of caffeine and anthropometric assessment was performed. Liver biopsy was performed in a maximum period of 36 months before inclusion in the study Results There were 113 patients, 67 (59.3%) females, 48 (42.5%) were aged between 52 and 62 years, and 101 (89.4%) were white. The average caffeine consumption was 251.41 ± 232.32 mg/day, and 70 (62%) patients consumed up to 250 mg/day of caffeine. There was no association between caffeine consumption and inflammatory activity on liver biopsy. On the other hand, when evaluating the caffeine consumption liver fibrosis an inverse association was observed. Conclusions The greater consumption of caffeine was associated with lower liver fibrosis. There was no association between caffeine consumption and inflammatory activity. .

Contexto O consumo de cafeína tem sido relacionado à diminuição dos níveis de enzimas hepáticas e menor risco de fibrose em pacientes portadores do vírus da hepatite C. Objetivo O presente estudo tem por objetivo avaliar a associação do consumo da cafeína com a atividade inflamatória e o grau de fibrose hepática em pacientes com infecção pelo vírus da hepatite C. Métodos Estudo transversal, constituído por pacientes com infecção pelo vírus da hepatite C atendidos no ambulatório de Gastroenterologia do Complexo Hospitalar Santa Casa (Porto Alegre - Brasil). Os pacientes foram entrevistados e avaliados individualmente quanto ao consumo de cafeína e antropometria. A biópsia hepática foi realizada em um período de no máximo 36 meses antes da inclusão no estudo. Resultados Foram avaliados 113 pacientes, sendo 67 (59,3%) do sexo feminino, 48 (42,5%) apresentavam idade entre 52 e 62 anos, e 101 (89,4%) eram de cor branca. O consumo médio de cafeína foi de 251,41 ± 232,32 mg/dia, sendo que 70 (62%) pacientes consumiam até 250 mg/dia de cafeína. Não houve associação entre o consumo de cafeína e a atividade inflamatória na biópsia hepática. Por outro lado, quando avaliada a associação entre o consumo de cafeína e fibrose hepática observou-se relação inversa. Conclusões O maior consumo de cafeína apresentou associação com menor grau de fibrose hepática. Não houve associação entre o consumo de cafeína e a atividade inflamatória. .

Coffee has hepatoprotective benefits in Brazilian patients with chronic hepatitis C even in lower daily consumption than in American and European populations

The potential role of coffee as a hepatoprotective substance for chronic liver diseases has been widely discussed. Our main aim was to evaluate the effect of coffee intake regarding clinical, biochemical tests and liver biopsy data in treatment naïve patients with chronic hepatitis C. One hundred and thirty-six patients with chronic hepatitis C, diagnosed through liver biopsy, or by means of clinical, ultrasound or endoscopic signs of cirrhosis, were assessed by determination of biochemical tests, metabolic and morphological alterations. Food frequency was scrutinized by using a structured questionnaire. Coffee intake represented more than 90% of the total daily caffeine, and the 75th percentile was 4-Brazilian coffee-cup/day (>255mL/day or >123mg caffeine/day). According to caffeine intake, patients were divided into two groups (< or >123mg caffeine/day). Patients with higher ingestion of caffeine had lower serum levels of aspartate aminotransferase (× upper limit of normal) (1.8±1.5 vs 2.3±1.5, p=0.04), lower frequencies of advanced (F3, F4) fibrosis (23.5% vs 54.5%, p<0.001) and of histological activity grade (A3, A4) observed in liver biopsies (13.8% vs 36.9%, p<0.001). By multivariate logistic regression, fibrosis was independently associated with caffeine intake (OR- 0.16; 95%CI - 0.03-0.80; p=0.026), γ-glutamil transferase serum levels and morphological activity. But only fibrosis was associated with histological activity. In conclusion caffeine consumption greater than 123mg/day was associated with reduced hepatic fibrosis. In addition, this study supports the assumption that coffee intake has hepatoprotective benefits for Brazilian patients with chronic hepatitis C, even in lower doses than that of American and European population intake.

Do differences exist between chronic hepatitis C genotypes 2 and 3?

Introduction Six genotypes of the hepatitis C virus (HCV) have been identified thus far, and their distribution is well defined. Genotype 1, which is the most prevalent worldwide, is always compared to genotypes 2 and 3, particularly in terms of treatment response. However, little is known about the differences between genotypes 2 and 3 because these genotypes are analyzed together in most studies. Therefore, the aim of this study was to evaluate differences in the clinical, epidemiological, laboratory, and histological parameters between HCV-2 and HCV-3. Methods Patients with chronic hepatitis C infected with genotypes 2 and 3 were studied retrospectively and compared according to clinical, laboratory, and histological aspects. Hepatitis C virus-ribonucleic acid (HCV-RNA) was analyzed quantitatively by TaqMan® real-time PCR, and the HCV genotype was determined by sequencing the 5′-untranslated region. Results A total of 306 patients with chronic HCV-2 (n=50) and HCV-3 (n = 256) were studied. Subtype 2b (n=17/50) and subtype 3a (n=244/256) were the most prevalent among patients infected with HCV-2 and HCV-3, respectively. The mean age was 47 ± 10 years, and there was a predominance of men in the group studied (61%). Comparative analysis between HCV-2 and HCV-3 showed a younger age (p=0.002), less prevalence of arterial hypertension (p=0.03), higher serum albumin levels (p=0.01), more advanced stage of liver fibrosis (p=0.03), and higher frequency of steatosis in patients with HCV-3 (p=0.001). After multivariate regression analysis, all the variables, except serum albumin, remained as variables associated with HCV-3 in the final model. Conclusions Clinical and histological differences exist between HCV-2 and HVC-3, which suggests the need for separate analyses of these genotypes. .

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction. .

ELF (Enhanced Liver Fibrosis) como marcador não invasivo de fibrose hepática na hepatite C crônica / ELF (Enhanced Liver Fibrosis) as a non invasive predictor of liver fibrosis in hepatitis C

A fibrose hepática é o aspecto mais relevante e o mais importante determinante de morbimortalidade na hepatite C crônica (HCC). Historicamente, a biópsia hepática é o método de referência para avaliação da fibrose causada pela HCC, apesar de apresentar limitações. O estudo de marcadores não invasivos, que possam obviar a necessidade da biópsia, é uma área de constante interesse na hepatologia. Idealmente, a avaliação da fibrose hepática deveria ser acurada, simples, prontamente disponível, de baixo custo e informar sobre o prognóstico da patologia. Os marcadores não invasivos mais estudados são a elastografia hepática transitória (EHT) e os laboratoriais. A EHT já foi extensamente validada na HCC e está inserida na rotina de avaliação destes pacientes. Dentre os laboratoriais, existem diversos testes em continua experimentação e, até o momento, nenhum foi integrado à prática clínica no Brasil, embora já aplicados rotineiramente em outros países. O Enhanced Liver Fibrosis (ELF), um teste que dosa no soro ácido hialurônico, pró-peptídeo amino-terminal do colágeno tipo III e inibidor tissular da metaloproteinase 1, tem se mostrado bastante eficaz na detecção de fibrose hepática significativa e de cirrose na HCC. Neste estudo o ELF teve o seu desempenho avaliado em relação a biópsia hepática e demonstrou apresentar boa acurácia na detecção tanto de fibrose significativa quanto de cirrose. Na comparação com a EHT apresentou acurácia semelhante para estes mesmos desfechos, com significância estatística. No entanto, foi observada uma superestimação da fibrose com a utilização dos pontos de corte propostos pelo fabricante. Este achado está em acordo com a literatura, onde não há consenso sobre o melhor ponto de corte a ser empregado na prática clínica. Com a ampliação da casuística foi possível propor novos pontos de corte, através da análise clássica, com a biópsia hepática como padrão ouro...

Liver fibrosis is the most relevant issue concerning chronic hepatitis C (CHC) and determines its prognosis. Historically, liver biopsy has been the reference method for evaluating fibrosis related to CHC, though it presents many drawbacks. There is a continuing interest in the development of non invasive markers capable of replacing liver biopsy. The ideal surrogate for fibrosis evaluation should be accurate, simple, low cost and yield prognostic information. So far, the most well known non invasive methods are transient hepatic elastography (TE) and laboratory panels. TE has already been extensively validated and is integrated in patients routine. There is plenty of laboratory panels in continuing evaluation and some are already integrated in daily practice abroad. In Brasil, until the present moment, it is not a reality. Enhanced Liver Fibrosis (ELF) panel comprises the serum concentration of hyaluronic acid, tissue inhibitor of matrix metalloproteinases-1, and aminoterminal propeptide of type III procollagen and has demonstrated good performance in detecting significant fibrosis and cirrhosis in CHC patients. In the present study ELF had it’s performance evaluated against liver biopsy and obtained satisfactory accuracy in detecting significant fibrosis and cirrhosis. In comparison to TE no statistically significant diference was observed, for the same endpoints mentioned before. However, the application of manufacturer’s cutoff points produced overestimation of fibrosis stages. These findings are in accordance with other author’s results, in that there is no consensus so far on the most adequate cutoff points for main clinical end points. Enlarging the data permited calculating new cutoff points, through the classical statistical approach, using liver biopsy as the gold standard...

Strong correlation by ultrasonography of hepatomegaly and the presence of co-infection in HIV/HCV cirrhotic patients

OBJECTIVES: Progression of hepatic fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C virus compared to hepatitis C virus mono-infected patients. This study aimed to compare ultrasound features and selected clinical and biochemical variables between patients with human immunodeficiency virus/hepatitis C virus co-infection (n = 16) versus hepatitis C virus mono-infection (n = 16). METHODS: Each patient underwent abdominal ultrasound, and a specific evaluation was performed in order to detect findings consistent with chronic liver disease. Characterization of spleen size, liver structural pattern, diameter of the portal, spleen, and mesenteric veins was based on classical ultrasound parameters. Propensity score was used for control of selection bias and performed using binary logistic regression to generate a score for each patient. The Fisher and Mann-Whitney tests were used to evaluate categorical variables and continuous variables, respectively. RESULTS: On univariate analysis right hepatic lobe size was larger in human immunodeficiency virus/hepatitis C virus patients (157.06 ± 17.56 mm) compared to hepatitis C virus mono-infected patients (134.94 ± 16.95 mm) (p = 0.0011). The left hepatic lobe was also significantly larger in human immunodeficiency virus/hepatitis C virus patients Cirrhosis (115.88 ±22.69 mm) versus hepatitis C virus mono-infected patients (95.06 ±24.18 mm) (p= 0.0177). Also, there was a strong correlation between hepatomegaly and co-infection (p=0.005). CONCLUSION: Human immunodeficiency virus infection was the primary variable influencing liver enlargement in this population. Hepatomegaly on ultrasound was more common among cirrhotic human immunodeficiency virus/hepatitis C virus co-infected patients than among cirrhotic hepatitis C virus mono-infected patients. This aspect is very important in the management of human immunodeficiency virus/hepatitis C virus co-infected patients, because screening for hepatocellular carcinoma is necessary in this population.

Progression of iiver fibrosis in monoinfected ptients by hepatitis c virus andd coinfected by hcv and human immunodeficiency virus

Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV) has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected) Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations. .

Contexto A progressão da fibrose hepática em pacientes coinfectados pelos vírus da hepatite C (VHC) e da imunodeficiência humana (VHC/HIV) tem sido mais estudada na última década. Estudos realizados antes da terapia antiretroviral de alta potência (HAART) sugerem que o HIV pode mudar a história natural da infecção pelo VHC, levando a uma progressão mais rápida da fibrose hepática. Objetivo Avaliar e comparar a progressão de fibrose em duas populações de pacientes (coinfectados VHC/HIV e monoinfectados VHC). Métodos Foram avaliados retrospectivamente 70 pacientes monoinfectados VHC e 26 coinfectados VHC/HIV nunca tratados para o VHC e que haviam realizado duas biopsias hepáticas seriadas. Não houve diferença na progressão de fibrose entre os dois grupos. Conclusão A evolução do grau de fibrose não foi pior nos pacientes coinfectados. A ausência de imunodepressão e o menor intervalo de tempo entre as biopsias no grupo de coinfectados são possíveis justificativas. .

Influência do polimorfismo genético de citocinas na hepatite C crônica em uma população do Rio de Janeiro / Influence of cytokine genetic polymorphism on chronic hepatitis C in a population of Rio de Janeiro

A infecção pelo vírus da hepatite C (VHC) é uma das mais comuns infecções ao redor do mundo. Aproximadamente, 20% dos pacientes infectados eliminam espontaneamente o vírus, porém a maioria dos indivíduos infectados desenvolve infecção crônica com amplo espectro de lesões hepáticas, desde inflamação leve até cirrose. A resposta imune do hospedeiro exerce grande influência sobre o desfecho da infecção pelo VHC. O objetivo deste trabalho foi analisar a influência dos polimorfismos genéticos de citocinas na susceptibilidade ou persistência da infecção por VHC e no clareamento espontâneo em uma amostra de pacientes da população do Rio de Janeiro (Brasil). Os polimorfismos genéticos das citocinas TNFA (-308), TGFB1 (codon 10 e 25), IL10 (-1082, -592), IL6 (-174) e IFNG (+874) foram analisados por PCR-SSP em 245 pacientes com hepatite C crônica (HCC), 41 pacientes que alcançaram o clareamento viral espontâneo e 189 indivíduos controle saudáveis. Além disso, os polimorfismos próximos ao gene da citocina IL28B (rs12979860, rs12980275 e rs8099917) foram analisados por PCR em tempo real em todos os grupos...

Hepatitis C virus infection is one of the most common blood-borne infections worldwide. Approximately, 20% of infected patients successfully eliminate the virus, whereas the majority of patients develop chronic infection with a wide spectrum of liver lesions, ranging from a minimal inflammation to cirrhosis. The host's immune response is an important correlate of HCV infection outcome and disease progression. The aim of this study was to explore the possibility of the inheritance of cytokine gene polymorphisms as a candidate for susceptibility to persistent HCV infection or HCV clearance in a sample of Rio de Janeiro (Brazil) population. Genetic polymorphisms in the cytokines TNFA (-308), TGFB1 (codon 10 and 25), IL10 (-1082, -592), IL6 (-174) and IFNG (+874) were analyzed by polymerase chain reaction-sequence-specific primer (SSP) in 245 chronic hepatitis C (HCC) patients, 41 spontaneous recovery (SR) patients and 189 healthy volunteers. Further, IL28B (rs12979860, rs12980275 and rs8099917) were assessed by real-time PCR in all groups...

Resultados del tratamiento de la hepatitis crónica por virus C en un hospital público, en Chile / Results of chronic hepatitis C treatment in a public hospital

Background: Chronic hepatitis C is an important health problem in Chile. In 2005, the Ministry of Health started a pilot treatment program with peg interferon and ribavirin, to be developed in public hospitals all over the country. Aim: To report the results ofhepatitis C treatment obtained at our institution. Patients and Methods: Between 2005 and 2009, 63 patients were referred for treatment. In all, the viral load and genotype were determined. Peg interferon alpha-2a or alpha-2b plus ribavirin were used for therapy for up to 48 weeks in genotypes (G) 1 or 4 or 24 weeks in genotypes 2 or 3. If at the end oftreatment, viral load measured by polymerase chain reaction (PCR) was negative, it was repeated 6 months later. A negative viral load at that time was considered a sustained viral response (SVR). Results: Among the 51 patients who started treatment, 42 (80.4%) were G1,1 was G2,1 was G4 and 7 were G3. A SVR was reached in 51.1% ofG 1 and 4 and in 87.5% in G 3 and 2. In a univariate analysis, the variables significantly associated with a positive viral response were the degree offibrosis and body mass index. Conclusions: These results are similar to those obtained in other international series, demonstrating that Hispanic ethnicity does not influence the response to treatment. Our good results could be explained by the excellent compliance of the patients to the treatment. A higher degree offibrosis and a higher BMI were associated with a poor response.